TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27099	81520;81521;81522	chr2:178564837;178564836;178564835	chr2:179429564;179429563;179429562
N2AB	25458	76597;76598;76599	chr2:178564837;178564836;178564835	chr2:179429564;179429563;179429562
N2A	24531	73816;73817;73818	chr2:178564837;178564836;178564835	chr2:179429564;179429563;179429562
N2B	18034	54325;54326;54327	chr2:178564837;178564836;178564835	chr2:179429564;179429563;179429562
Novex-1	18159	54700;54701;54702	chr2:178564837;178564836;178564835	chr2:179429564;179429563;179429562
Novex-2	18226	54901;54902;54903	chr2:178564837;178564836;178564835	chr2:179429564;179429563;179429562
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-85
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.2844
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
D/G	None	None	0.978	N	0.57	0.504	0.397540356873	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
D/Y	rs1320967672	None	0.999	D	0.743	0.403	0.696367886986	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
D/A	0.6511	likely_pathogenic	0.6587	pathogenic	-0.216	Destabilizing	0.989	D	0.635	neutral	N	0.496020406	None	None	I
D/C	0.9052	likely_pathogenic	0.9061	pathogenic	0.137	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
D/E	0.7692	likely_pathogenic	0.756	pathogenic	-0.746	Destabilizing	0.948	D	0.472	neutral	N	0.498298131	None	None	I
D/F	0.9474	likely_pathogenic	0.9465	pathogenic	-0.521	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	I
D/G	0.5676	likely_pathogenic	0.5799	pathogenic	-0.474	Destabilizing	0.978	D	0.57	neutral	N	0.514164341	None	None	I
D/H	0.7387	likely_pathogenic	0.7603	pathogenic	-0.905	Destabilizing	0.997	D	0.709	prob.delet.	N	0.502047567	None	None	I
D/I	0.879	likely_pathogenic	0.8867	pathogenic	0.426	Stabilizing	0.999	D	0.757	deleterious	None	None	None	None	I
D/K	0.8793	likely_pathogenic	0.8925	pathogenic	0.043	Stabilizing	0.983	D	0.603	neutral	None	None	None	None	I
D/L	0.8804	likely_pathogenic	0.8804	pathogenic	0.426	Stabilizing	0.998	D	0.741	deleterious	None	None	None	None	I
D/M	0.9434	likely_pathogenic	0.9482	pathogenic	0.866	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
D/N	0.123	likely_benign	0.1241	benign	-0.21	Destabilizing	0.198	N	0.187	neutral	N	0.48236886	None	None	I
D/P	0.9361	likely_pathogenic	0.9441	pathogenic	0.237	Stabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	I
D/Q	0.8736	likely_pathogenic	0.88	pathogenic	-0.153	Destabilizing	0.998	D	0.68	prob.neutral	None	None	None	None	I
D/R	0.8759	likely_pathogenic	0.9003	pathogenic	-0.076	Destabilizing	0.998	D	0.731	prob.delet.	None	None	None	None	I
D/S	0.2811	likely_benign	0.2822	benign	-0.358	Destabilizing	0.983	D	0.576	neutral	None	None	None	None	I
D/T	0.4241	ambiguous	0.4406	ambiguous	-0.152	Destabilizing	0.983	D	0.598	neutral	None	None	None	None	I
D/V	0.752	likely_pathogenic	0.7615	pathogenic	0.237	Stabilizing	0.999	D	0.755	deleterious	N	0.517669833	None	None	I
D/W	0.9883	likely_pathogenic	0.9898	pathogenic	-0.561	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
D/Y	0.6566	likely_pathogenic	0.6872	pathogenic	-0.319	Destabilizing	0.999	D	0.743	deleterious	D	0.537041536	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.